Pract Neurol doi:10.1136/practneurol-2012-000473
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Coagulation of cerebrospinal fluid—the Nonne–Froin sign

  1. Henrik Zetterberg1,5
  1. 1Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
  2. 2Geriatric Clinic, Gävle County Hospital, Gavle, Sweden
  3. 3Department of Neuroscience, Neurosurgery, Uppsala University Hospital, Uppsala, Sweden
  4. 4The Medical History Museum, Göteborg, Gothenburg, Sweden
  5. 5UCL Institute of Neurology, London, UK
  1. Correspondence to Dr Niklas Mattsson, Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital/Mölndal, University of Gothenburg, Mölndal 431 80, Sweden; niklas.mattsson{at}

A 60-year-old previously healthy woman sought medical attention at a memory clinic for subjective cognitive impairment. Neurological and cognitive testing was normal, except that she performed at the lower limit of normal in A Quick Test of Cognitive Speed (AQT) and Rey complex figure tests. MRI of the brain was normal. As a part of the investigation she underwent lumbar puncture, a routine procedure in memory investigations in Sweden.

The cerebrospinal fluid (CSF) was found to be yellow and viscous. The CSF flow through the lumbar puncture needle was slow and did not increase when pressure was applied on the external jugular veins. The CSF albumin concentration was elevated at 31 g/l (normal <0.42) and the CSF/serum albumin ratio was markedly increased at 0.73 (normal <0.010). The CSF white cell count was normal at 2/µl (<6) and the red cell count was only slightly elevated (173/µl; normal <5). MRI of the spine showed an intradural tumour, filling the spinal canal from vertebrae L1 to L4.

On further discussion, she gave a history of lumbar back pain and difficulties emptying her bladder. She was referred for neurosurgery: the tumour was removed and found to be an ependymoma. At follow-up 9 months after surgery, she was in general good health, with no cognitive problems and was back at work.


Discolouration and coagulation of CSF (figure 1) was first described in meningitis by Georges Froin (1874–1932) and in spinal tumours by Max Nonne (1860–1959). This early history has been extensively reviewed and referenced by Greenfield.1 The CSF changes are due to passive inflow of plasma proteins (including fibrinogen) from the blood to the stagnated CSF below the obstruction. There are case reports of spinal tumours associated with hydrocephalus and cognitive impairment.2 ,3 However, the absence of hydrocephalus in our patient makes a link between the spinal tumour and the presenting cognitive symptoms unlikely. We consider finding the spinal tumour while investigating memory symptoms serendipitous.

Figure 1

Xanthochromia and coagulation of cerebrospinal fluid (CSF) with elevated plasma protein content (arrow, as compared with normal CSF, *). The photograph was taken using a Haag–Streit slit lamp equipped with a Canon 40D digital camera.


We thank photographer Anna-Maria Timbus at the Eye Clinic, Sahlgrenska University Hospital, for taking the photo.


  • Contributors NM drafted the paper. RM and AH managed the patient and collected clinical data. RM, AH, LM, KB and HZ revised the paper for intellectual content.

  • Competing interests None.

  • Ethics approval University of Gothenburg ethical committee.

  • Provenance and peer review Not commissioned. Externally peer reviewed. This paper was reviewed by Brendan McLean, Truro, UK.


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